{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:05:56Z","timestamp":1785405956156,"version":"3.56.0"},"reference-count":59,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"name":"United States Government"},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Alpha-klotho is a circulating protein linked to better metabolic and aging-related outcomes. However, alpha-klotho's relationship with insulin resistance, and the role of adiposity, remain unclear, especially among older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association of circulating alpha-klotho with measures of insulin resistance and incident diabetes among older adults and examine whether these relationships differ by body mass index (BMI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>The primary outcome was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Secondary outcomes were serum fasting glucose and insulin, and incident diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, and participants<\/jats:title>\n                    <jats:p>This secondary analysis examined associations of alpha-klotho with outcomes among 825 community-dwelling adults aged \u226555 years enrolled in the Invecchiare in Chianti Study, a prospective population-based cohort. Alpha-klotho and outcomes were assessed 3 years after enrollment. We performed BMI-stratified regression analysis, with adjustment for covariates, including measures of glucose and insulin taken at enrollment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 370 overweight participants (BMI 25.0-29.9\u2005kg\/m2), each logarithm unit of alpha-klotho (pg\/mL) was associated with 0.51 higher HOMA-IR (95% confidence interval [CI], 0.07-0.94), after covariate adjustment. Alpha-klotho was significantly associated with serum glucose (Beta = 0.56, 95% CI: 0.04-1.09), but not serum insulin after covariate adjustment. No significant associations were found among participants with BMI &amp;lt; 25.0 (n = 279) or \u226530\u2005kg\/m2 (n = 124) (P for interaction = 0.18). Alpha-klotho was not significantly associated with incident diabetes, overall or in any BMI subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Alpha-klotho was positively associated with insulin resistance, but not incident diabetes, among overweight adults. Findings suggest that alpha-klotho may have a context-dependent relationship with insulin resistance, but not incident diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvag140","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:42:39Z","timestamp":1781955759000},"source":"Crossref","is-referenced-by-count":1,"title":["Alpha-klotho, insulin resistance, and adiposity among older adults"],"prefix":"10.1210","volume":"10","author":[{"given":"Anam","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5283-2082","authenticated-orcid":false,"given":"Michelle","family":"Shardell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-6884","authenticated-orcid":false,"given":"Rita Rastogi","family":"Kalyani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Semba","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braxton D","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]},{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4161-3829","authenticated-orcid":false,"given":"Toshiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"National Institute on Aging, National Institutes of Health , Baltimore, MD 21224 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-7854","authenticated-orcid":false,"given":"Simeon","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]},{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of 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